tbuckley/cabot-search huggingface dataset:
Lignin-assisted construction of sub-10 nm supramolecular self-assembly for photothermal immunotherapy and potentiating anti-PD-1 therapy against primary and distant breast tumors
Authors: Xudong Fan, Tianxiang Yue, Aidi Liu, Xiaowei Xie, Weixiang Fang, Yinghui Wei, Hangsheng Zheng, Hongyue Zheng, Meiqi Zhou, Jigang Piao, Fanzhu Li
Journal: Asian Journal of Pharmaceutical Sciences (2022)

Photothermal therapy (PTT) has brought hope for cancer treatments, with hyperthermia-induced immunogenic cell death (ICD), which is a critical part of therapeutically induced antitumor immune responses. Limited immune stimulation response in PTT is the primary reason for incomplete tumor ablation, therefore demonstrating urgent requirements for ICD amplifier. Herein, a sub-10 nm supramolecular nanoassembly was formed by co-assembly of clinically approved aluminum adjuvant and commonly used indocyanine green (ICG) under the assistance of lignosulfonate (LS, a green and sustainable multifunctional lignin derivative) for localized photothermal-immunotherapy of breast cancer. The overall results revealed that LS-Al-ICG is capable of inducing amplified ICD, efficiently eliciting solid immune responses through dendritic cells (DCs) activation and cytotoxic T-cell responses initiation for tumor killing. Moreover, anti-PD-1 therapy blocked the PD-1 pathway and led to remarkable anti-tumor efficacy against laser-irradiated primary tumors and distant tumors by potentiating systemic tumor specific T cell immunity. The results of this study demonstrate a handy and extensible approach for engineering green natural lignin nanoparticles for cancer immunotherapy, which shows promise for delivering other therapeutics in biomedical applications.
Oesophageal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up
Authors: R. Obermannová, M. Alsina, A. Cervantes, T. Leong, F. Lordick, M. Nilsson, N.C.T. van Grieken, A. Vogel, E.C. Smyth
Journal: Annals of Oncology (2022)
COVID-19 vaccination and BA.1 breakthrough infection induce neutralising antibodies which are less efficient against BA.4 and BA.5 Omicron variants, Israel, March to June 2022
Authors: Limor Kliker, Neta Zuckerman, Nofar Atari, Noam Barda, Mayan Gilboa, Ital Nemet, Bayan Abd Elkader, Ilana S Fratty, Hanaa Jaber, Ella Mendelson, Sharon Alroy-Preis, Yitshak Kreiss, Gili Regev-Yochay, Michal Mandelboim
Journal: Eurosurveillance (2022)

This work evaluated neutralising antibody titres against wild type (WT) SARS-CoV-2 and four Omicron variants (BA.1, BA.2, BA.4 and BA.5) in healthcare workers who had breakthrough BA.1 infection. Omicron breakthrough infection in individuals vaccinated three or four times before infection resulted in increased neutralising antibodies against the WT virus. The fourth vaccine dose did not further improve the neutralising efficiency over the third dose against all Omicron variants, especially BA.4 and BA.5. An Omicron-specific vaccine may be indicated.
The Impact of Exposure Measurement Error on the Estimated Concentration–Response Relationship between Long-Term Exposure to PM2.5 and Mortality
Authors: Yaguang Wei, Xinye Qiu, Mahdieh Danesh Yazdi, Alexandra Shtein, Liuhua Shi, Jiabei Yang, Adjani A. Peralta, Brent A. Coull, Joel D. Schwartz
Journal: Environmental Health Perspectives (2022)

Background: Exposure measurement error is a central concern in air pollution epidemiology. Given that studies have been using ambient air pollution predictions as proxy exposure measures, the potential impact of exposure error on health effect estimates needs to be comprehensively assessed. Objectives: We aimed to generate wide-ranging scenarios to assess direction and magnitude of bias caused by exposure errors under plausible concentration–response relationships between annual exposure to fine particulate matter [PM ≤2.5μm in aerodynamic diameter (PM2.5)] and all-cause mortality. Methods: In this simulation study, we use daily PM2.5 predictions at 1-km2 spatial resolution to estimate annual PM2.5 exposures and their uncertainties for ZIP Codes of residence across the contiguous United States between 2000 and 2016. We consider scenarios in which we vary the error type (classical or Berkson) and the true concentration–response relationship between PM2.5 exposure and mortality (linear, quadratic, or soft-threshold—i.e., a smooth approximation to the hard-threshold model). In each scenario, we generate numbers of deaths using error-free exposures and confounders of concurrent air pollutants and neighborhood-level covariates and perform epidemiological analyses using error-prone exposures under correct specification or misspecification of the concentration–response relationship between PM2.5 exposure and mortality, adjusting for the confounders. Results: We simulate 1,000 replicates of each of 162 scenarios investigated. In general, both classical and Berkson errors can bias the concentration–response curve toward the null. The biases remain small even when using three times the predicted uncertainty to generate errors and are relatively larger at higher exposure levels. Discussion: Our findings suggest that the causal determination for long-term PM2.5 exposure and mortality is unlikely to be undermined when using high-resolution ambient predictions given that the estimated effect is generally smaller than the truth. The small magnitude of bias suggests that epidemiological findings are relatively robust against the exposure error. In practice, the use of ambient predictions with a finer spatial resolution will result in smaller bias. https://doi.org/10.1289/EHP10389
Length of stay in Denmark before HIV diagnosis and linkage to care: a population-based study of migrants living with HIV, Denmark, 1995 to 2020
Authors: Olivia Borchmann, Lars Haukali Omland, Jan Gerstoft, Carsten Schade Larsen, Isik Somuncu Johansen, Suzanne Lunding, Janne Jensen, Niels Obel, Ann-Brit Eg Hansen
Journal: Eurosurveillance (2022)

BackgroundMigrants face an increased risk of HIV infection and late presentation for HIV care.AimTo examine delays in HIV diagnosis, linkage to care (LTC), and risk of late presentation for migrants living with HIV in Denmark.MethodsWe conducted a population-based, nationwide study of adult migrants (n = 2,166) presenting for HIV care between 1 January 1995 and 31 December 2020 in Denmark. Time from immigration to HIV diagnosis and from diagnosis to LTC, and late presentation were assessed, stratified by migrants' geographical regions of origin, using descriptive statistics.ResultsThe demographics of the migrant population changed over time. Overall, migrants diagnosed with HIV after immigration to Denmark resided a median of 3.7 (IQR: 0.8-10.2) years in Denmark before diagnosis. Median time from HIV diagnosis to LTC was 6 (IQR: 0-24) days. Migrants diagnosed with HIV infection before immigration had a median of 38 (IQR: 0-105) days from arrival in Denmark to LTC. The corresponding median times for 2015-20 alone were 4.1 (IQR: 0.9-13.1) years, 0 (IQR: 0-8) days, and 62 (IQR: 25-152) days, respectively. The overall proportion of late presentation among migrants diagnosed with HIV after immigration was 60%, and highest among migrants from sub-Saharan Africa and East and South Asia.ConclusionHIV diagnosis is still substantially delayed in Danish migrants, while LTC is timely. The proportions with late presentation are high. These results call for targeted interventions to reduce the number of migrants with undiagnosed HIV infections and of late presenters.
Efficacy and safety of tirzepatide monotherapy compared with dulaglutide in Japanese patients with type 2 diabetes (SURPASS J-mono): a double-blind, multicentre, randomised, phase 3 trial
Authors: Nobuya Inagaki, Masakazu Takeuchi, Tomonori Oura, Takeshi Imaoka, Yutaka Seino
Journal: The Lancet Diabetes & Endocrinology (2022)
CX3CL1/CX3CR1 interaction protects against lipotoxicity-induced nonalcoholic steatohepatitis by regulating macrophage migration and M1/M2 status
Authors: Yinhua Ni, Fen Zhuge, Liyang Ni, Naoto Nagata, Tatsuya Yamashita, Naofumi Mukaida, Shuichi Kaneko, Tsuguhito Ota, Mayumi Nagashimada
Journal: Metabolism (2022)
Hormonal contraception and risk of breast cancer and breast cancer in situ among Swedish women 15–34 years of age: A nationwide register-based study
Authors: Jenny Niemeyer Hultstrand, Kristina Gemzell-Danielsson, Helena Kopp Kallner, Henrik Lindman, Per Wikman, Inger Sundström-Poromaa
Journal: The Lancet Regional Health - Europe (2022)

Evidence on a possible association between newer hormonal contraceptives (HC) and risk of breast cancer remains inconclusive, especially as concerns progestogen-only methods. In this nationwide prospective cohort study, all Swedish women aged 15–34 at study start on January 1st 2005, or who turned 15 years during the study period, were followed until December 31st 2017. Using information from seven National Registers, we assessed the risk ratio of developing breast cancer and breast cancer in situ in relation to different HC using Poisson regression. We adjusted the analyses for several known confounders of breast cancer. This cohort included 1.5 million women providing more than 14 million person-years. During the study period, 3842 women were diagnosed with breast cancer. Compared with never users of any HC, we found no increased risk of developing breast cancer among current users of any combined HC, IRR 1.03 (0.91–1.16), whereas current users of progestogen-only methods had an increased risk of developing breast cancer, IRR 1.32 (1.20–1.45). Across all types of HC, the risk of developing breast cancer appeared to be highest the first five years of use (combined HC IRR 1.39 (1.14–1.69); progestogen-only methods IRR 1.74 (1.44–2.10). The risk disappeared ten years after the women stopped using HC. The absolute risk of breast cancer per 100,000 women-years was 22.4 for never users, 10.9 for current users of combined HC, and 29.8 for current users of progestogen-only methods. Current use of progestogen-only methods is associated with a small increased risk of developing breast cancer, whereas we could only detect an increased risk among users of combined HC during the first five years of use. This may partly be explained by a selective prescription of progestogen-only methods to women with risk factors for breast cancer, like smoking or obesity. As the absolute risk of breast cancer was small, the many health benefits associated with HC must also be taken into account in contraceptive counselling. This study was funded by the Swedish Cancer Society and by the Uppsala County Council, the Faculty of Medicine at Uppsala University.
Equity of access to NHS-funded hip replacements in England and Wales: Trends from 2006 to 2016
Authors: Steven Wyatt, Rowena Bailey, Patrick Moore, Matthew Revell
Journal: The Lancet Regional Health - Europe (2022)

Elective hip replacement is a cost-effective means of improving hip function. Previous research has suggested that the supply of hip replacements in the NHS is governed by the inverse care law. We examine whether inequities in supply improved in England and Wales between 2006 and 2016.We compare levels of need and supply of NHS funded hip replacements to adults aged 50+ years, across quintiles of deprivation in England and Wales between 2006 and 2016. We use data from routine health records and a large longitudinal study and adjust for age and sex using general additive negative-binomial regression.The number of NHS-funded hip replacements per 100,000 population rose substantially from 272.6 and 266.7 in 2002, to 539.7 and 466.3 in 2018 in England and Wales respectively. Having adjusted for age and sex, people living in the most deprived quintile were 2.36 (95% CI, 1.69 to 3.29) times more likely to need a hip replacement in 2006 than those living in quintile 3, whereas those living in the least deprived quintile were 0.45 (95% CI, 0.39 to 0.69) as likely. Despite this, people living in the most deprived quintile were 0.81 (95% CI, 0.78 to 0.83) times as likely in England and 0.93 (95% CI, 0.84 to 1.04) as likely in Wales to receive an NHS-funded hip replacement in 2006 than those living in quintile 3. We found no evidence that these substantial inequities had reduced between 2006 and 2016.With respect to hip-replacement surgery in England and Wales, policy ambitions to reduce healthcare inequities have not been realised.This work was supported by Health Data Research UK.
Identification of a Gain-of-Function <i>LIPC</i> Variant as a Novel Cause of Familial Combined Hypocholesterolemia
Authors: Wieneke Dijk, Mathilde Di Filippo, Sander Kooijman, Robin van Eenige, Antoine Rimbert, Amandine Caillaud, Aurélie Thedrez, Lucie Arnaud, Amanda Pronk, Damien Garçon, Thibaud Sotin, Pierre Lindenbaum, Enrique Ozcariz Garcia, Jean-Paul Pais de Barros, Laurence Duvillard, Karim Si-Tayeb, Nuria Amigo, Jean-Yves Le Questel, Patrick C.N. Rensen, Cédric Le May, Philippe Moulin, Bertrand Cariou
Journal: Circulation (2022)

Background: Atherosclerotic cardiovascular disease is the main cause of mortality worldwide and is strongly influenced by circulating low-density lipoprotein (LDL) cholesterol levels. Only a few genes causally related to plasma LDL cholesterol levels have been identified so far, and only 1 gene, ANGPTL3 , has been causally related to combined hypocholesterolemia. Here, our aim was to elucidate the genetic origin of an unexplained combined hypocholesterolemia inherited in 4 generations of a French family. Methods: Using next-generation sequencing, we identified a novel dominant rare variant in the LIPC gene, encoding for hepatic lipase, which cosegregates with the phenotype. We characterized the impact of this LIPC -E97G variant on circulating lipid and lipoprotein levels in family members using nuclear magnetic resonance–based lipoprotein profiling and lipidomics. To uncover the mechanisms underlying the combined hypocholesterolemia, we used protein homology modeling, measured triglyceride lipase and phospholipase activities in cell culture, and studied the phenotype of APOE*3.Leiden.CETP mice after LIPC -E97G overexpression. Results: Family members carrying the LIPC -E97G variant had very low circulating levels of LDL cholesterol and high-density lipoprotein cholesterol, LDL particle numbers, and phospholipids. The lysophospholipids/phospholipids ratio was increased in plasma of LIPC -E97G carriers, suggestive of an increased lipolytic activity on phospholipids. In vitro and in vivo studies confirmed that the LIPC -E97G variant specifically increases the phospholipase activity of hepatic lipase through modification of an evolutionarily conserved motif that determines substrate access to the hepatic lipase catalytic site. Mice overexpressing human LIPC -E97G recapitulated the combined hypocholesterolemic phenotype of the family and demonstrated that the increased phospholipase activity promotes catabolism of triglyceride-rich lipoproteins by different extrahepatic tissues but not the liver. Conclusions: We identified and characterized a novel rare variant in the LIPC gene in a family who presents with dominant familial combined hypocholesterolemia. This gain-of-function variant makes LIPC the second identified gene, after ANGPTL3 , causally involved in familial combined hypocholesterolemia. Our mechanistic data highlight the critical role of hepatic lipase phospholipase activity in LDL cholesterol homeostasis and suggest a new LDL clearance mechanism.
Estimation of COVID-19 vaccine effectiveness against hospitalisation in individuals aged ≥ 65 years using electronic health registries; a pilot study in four EU/EEA countries, October 2021 to March 2022
Authors: Alexis Sentís, Irina Kislaya, Nathalie Nicolay, Hinta Meijerink, Jostein Starrfelt, Iván Martínez-Baz, Jesús Castilla, Katrine Finderup Nielsen, Christian Holm Hansen, Hanne-Dorthe Emborg, Anthony Nardone, Tarik Derrough, Marta Valenciano, Baltazar Nunes, Susana Monge
Journal: Eurosurveillance (2022)

By employing a common protocol and data from electronic health registries in Denmark, Navarre (Spain), Norway and Portugal, we estimated vaccine effectiveness (VE) against hospitalisation due to COVID-19 in individuals aged ≥ 65 years old, without previous documented infection, between October 2021 and March 2022. VE was higher in 65-79-year-olds compared with ≥ 80-year-olds and in those who received a booster compared with those who were primary vaccinated. VE remained high (ca 80%) between ≥ 12 and < 24 weeks after the first booster administration, and after Omicron became dominant.
High antimicrobial resistance in urinary tract infections in male outpatients in routine laboratory data, Germany, 2015 to 2020
Authors: Jonas Salm, Florian Salm, Patricia Arendarski, Tobias Siegfried Kramer
Journal: Eurosurveillance (2022)

Background Evidence on the distribution of bacteria and therapy recommendations in male outpatients with urinary tract infections (UTI) remains insufficient. Aim We aimed to report frequency distributions and antimicrobial resistance (AMR) of bacteria causing UTI in men and to identify risk factors for resistance of Escherichia coli against trimethoprim (TMP) and ciprofloxacin (CIP). Methods We conducted a retrospective observational study using routinely collected midstream urine specimens from 102,736 adult male outpatients sent from 6,749 outpatient practices to nine collaborating laboratories from all major regions in Germany between 2015 and 2020. Resistance in E. coli was predicted using logistic regression. Results The three most frequent bacteria were E. coli (38.4%), Enterococcus faecalis (16.5%) and Proteus mirabilis (9.3%). Resistance of E. coli against amoxicillin (45.7%), TMP (26.6%) and CIP (19.8%) was common. Multiple drug resistance was high (22.9%). Resistance against fosfomycin (0.9%) and nitrofurantoin (1.9%) was low. Resistance of En. faecalis against CIP was high (29.3%). Isolates of P. mirabilis revealed high resistance against TMP (41.3%) and CIP (16.6%). The CIP and TMP resistance was significantly higher among bacteria derived from recurrent UTI (p &lt; 0.05). Age ≥ 90 years, recurrent UTI and regions East and South were independently associated with AMR of E. coli against TMP and CIP (p &lt; 0.05). Conclusion The most frequent UTI-causing pathogens showed high resistance against TMP and CIP, empirical therapy is therefore likely to fail. Apart from intrinsically resistant pathogens, susceptibility to fosfomycin and nitrofurantoin remains sufficient. Therefore, they remain an additional option for empirical treatment of uncomplicated UTI in men.
Droplet digital PCR for the detection of second-generation tyrosine kinase inhibitor-resistant BCR::ABL1 kinase domain mutations in chronic myeloid leukemia
Authors: Simona Soverini, Sara De Santis, Margherita Martelli, Cecilia Monaldi, Fausto Castagnetti, Gabriele Gugliotta, Cristina Papayannidis, Manuela Mancini, Samantha Bruno, Claudia Venturi, Katerina Machova Polakova, Thomas Ernst, Dianna Maar, Adam Corner, Michele Cavo
Journal: Leukemia (2022)
Oral delivery of camptothecin-loaded multifunctional chitosan-based micelles is effective in reduce colorectal cancer
Authors: Andreia Almeida, Flávia Castro, Carlos Resende, Marlene Lúcio, Simó Schwartz, Bruno Sarmento
Journal: Journal of Controlled Release (2022)

Colorectal cancer (CRC) is a heterogeneous disease with high incidence and mortality worldwide. The efficacy of conventional CRC chemotherapy is hampered by poor drug solubility and bioavailability and suboptimal pharmacokinetic profiles. In this work, camptothecin (CPT), a potent anticancer drug, was loaded into an amphiphilic chitosan modified with PEG and oleic acid, to reduce CRC progression after oral administration. While CPT-loaded micelles presented anticancer activity against HCT116, Caco-2 and HT29 CRC cell lines in vitro, empty micelles demonstrated a safe profile when incubated with human blood cells and colorectal cancer cell lines. In a more complex 3D CRC multicellular spheroid model, CPT-loaded micelles also exhibited a significant effect on the spheroid's metabolic activity and size reduction. Remarkably, in vivo studies performed in a HCT116 xenograft model, showed a significant reduction on the tumor growth during and after treatment with CPT-loaded micelles. Moreover, in a more biological relevant in vivo model of chemically-induced CRC, orally administered CPT-loaded micelles demonstrated a significant reduction on tumor incidence and inflammation signs. The findings here reported indicate that CPT-loaded into chitosan-based micelles, by improving drug solubility, alongside its safety profile for normal tissues, may have a promising role CRC chemotherapy.
MicroRNA delivery systems in glioma therapy and perspectives: A systematic review
Authors: José Marcos Jiménez-Morales, Yanet Elisa Hernández-Cuenca, Ander Reyes-Abrahantes, Henry Ruiz-García, Francisco Barajas-Olmos, Humberto García-Ortiz, Lorena Orozco, Alfredo Quiñones-Hinojosa, Jesús Reyes-González, María del Carmen Abrahantes-Pérez
Journal: Journal of Controlled Release (2022)

Gliomas are the deadliest of all primary brain tumors, and they constitute a serious global health problem. MicroRNAs (miRNAs) are gene expression regulators associated with glioma pathogenesis. Thus, miRNAs represent potential therapeutic agents for treating gliomas. However, miRNAs have not been established as part of the regular clinical armamentarium. This systemic review evaluates current molecular and pre-clinical studies with the aim of defining the most appealing supramolecular platform for administering therapeutic miRNA to patients with gliomas. An integrated analysis suggested that cationic lipid nanoparticles, functionalized with octa-arginine peptides, represent a potentially specific, practical, non-invasive intervention for treating gliomas. This supramolecular platform allows loading both hydrophilic (miRNA) and hydrophobic (anti-tumor drugs, like temozolomide) molecules. This systemic review is the first to describe miRNA delivery systems targeted to gliomas that integrate several types of molecules as active ingredients. Further experimental validation is warranted to confirm the practical value of miRNA delivery systems.